Life-Threatening Microangiopathy or Vitamin Deficiency: A Case Report of the Clinical Manifestations of Pseudo-Thrombotic Microangiopathic Anemia.

Hemolytic anemia with thrombocytopenia and organ damage raises suspicion for thrombotic microangiopathy (TMA), a pathology that results in thrombosis within the small vessels secondary to endothelial injury. While usually attributed to atypical hemolytic uremic syndrome (aHUS) or thrombotic thrombocytopenic purpura (TTP), an increasingly recognized and treatable entity is pseudo-thrombotic microangiopathic anemia (pseudo-TMA) secondary to severe vitamin B-12 deficiency. While TMA often requires expensive diagnostic testing and can lead to invasive treatment options such as plasma exchange, immunosuppression, and/or complement cascade blocking, pseudo-TMA requires only vitamin supplementation. Therefore, the prompt and accurate diagnosis of this entity is important for the clinician to recognize in order to avoid unnecessary health costs and institute appropriate treatment. We present the case of a 51-year-old male without any past medical history, who presented with generalized weakness, dyspnea on exertion, and decreased exercise tolerance for several months and was found to have severe microangiopathic anemia with work-up concerning for TTP. After stabilization, he was found to have severe B-12 deficiency secondary to newly diagnosed pernicious anemia and was treated with subcutaneous B-12 injections with improvement in clinical symptoms and laboratory parameters. This presentation highlights the need for prompt diagnosis and high clinical suspicion for vitamin deficiencies as a source of pseudo-microangiopathy.

Phase II trial of gemcitabine/carboplatin followed by paclitaxel in patients with performance status=2,3 or other significant co-morbidity (HIV infection or s/p organ transplantation) in advanced non-small cell lung cancer.

INTRODUCTION: The role of chemotherapy in patients with advanced non-small cell lung cancer and poor performance status or who have HIV disease or organ transplantation is unclear. While survival appears to be enhanced, serious toxicity may occur. We evaluated the efficacy of sequential, dose attenuated carboplatin/gemcitabine followed by paclitaxel in patients with PS=2,3, HIV infection or after solid organ transplantation. PATIENTS AND METHODS: Chemotherapy naive patients with PS 2,3 or who were HIV positive or post solid organ transplantation were eligible. Treatment consisted of gemcitabine: 1000 mg/m(2) d 1,8 carboplatin: AUC=5 d 1 q 21d x 2 followed by paclitaxel 80 mg/m(2) q wk x 6 followed by a 2 week break and then repeated until progression. RESULTS: 47 patients were entered. Stage IIIb/IV: 8/39, PS 2/3=26/19, HIV infection=2, solid organ transplantation=2. 12 (25%) had brain metastases. Thirty-nine patients completed two cycles of carboplatin/gemcitabine and 29 pts received at least one cycle of paclitaxel. Overall response rate was 19% (95% CI 1.2-31.7%). Median event free, overall and 1-year survivals were 3.3 months, 5.8 months and 8.4%. Toxicity was moderate with 19% experiencing grade 4 neutropenia (11% with febrile neutropenia). CONCLUSIONS: Sequential carboplatin/gemcitabine to paclitaxel is well tolerated and active in this population. The survival seen is comparable to that of other regimens utilized in PS=2 patients with superior tolerability however, the prognosis for these patients is very poor even with treatment. This is the first trial to prospectively evaluate chemotherapy for patients with HIV disease or organ transplantation and NSCLC.

Lung cancer in HIV-infected patients in the era of highly active antiretroviral therapy.

BACKGROUND: Infection with the human immunodeficiency virus (HIV) and lung cancer represent two problems beginning in the 20th century that are of epidemic proportions. By the end of the 20th century, therapeutic programs of modest efficacy had been developed for both. Because both HIV infection and lung cancer are common, it is not surprising that a number of patients would be afflicted with both diseases simultaneously. There is a very limited literature regarding the treatment and outcome of patients with both diseases, particularly since the advent of highly active antiretroviral therapy (HAART) for HIV infection. METHODS: We retrospectively reviewed our tumor registry to ascertain cases with concurrent lung cancer and HIV diagnoses since 1996, at the advent of HAART. Twenty-nine patients were identified at the University of Maryland, and five additional cases from an affiliated institution were identified. RESULTS: Thirty patients had non-small cell lung cancer, and four patients had small cell lung cancer. Of the 30 patients with non-small cell lung cancer, 27 had stage IIIb/IV disease and were analyzed for outcome on the basis of CD4 counts and HAART therapy. Patients with CD4 counts >200 or those on HAART had numerically, though not statistically, superior survival. Patients were able to receive standard chemotherapy regimens, and the overall survival was 5.2 months. CONCLUSIONS: This single-institution analysis appears to indicate that there is an increasing incidence of patients with lung cancer and HIV infection. Patients with advanced NSCLC who are HIV positive with CD4 counts >200 can be treated with chemotherapy and demonstrate survival comparable to that of patients without HIV infection.

Lung cancer in women: emerging differences in epidemiology, biology, and therapy.

Lung cancer is the major cause of cancer-related death in both men and women in the United States. Emerging evidence indicates that there are differences in the pathogenesis and possibly increased susceptibility to lung cancer in women. In addition, considerable data support small, but important differences favoring women in terms of response to therapy and long-term survival after the diagnosis of lung cancer, regardless of histology or stage. These differences in both biology and outcome will be important considerations in the design of future trials of screening and therapy for lung cancer.

Double minute chromosomes in monoblastic (M5) and myeloblastic (M2) acute myeloid leukemia: two case reports and a review of literature.

Double minutes (dmin) are small, paired chromatin bodies that lack a centromere and represent a form of extrachromosomal gene amplification. Although they have been found in a variety of solid tumors, their presence in hematological malignancies, especially acute myeloid leukemia (AML), is rare. In addition, the presence of dmin may be a mechanism for upregulated oncogene expression and is generally associated with a poor prognosis. We describe two patients who had dmin at initial presentation of AML, including the first case of M5a with C-MYC amplification on dmin, and another case with C-MYC amplification as the only cytogenetic finding. We review here a total of 33 cases with dmin in AML. C-MYC was amplified by the dmin in 25 cases, while other putative oncogenes were amplified in the other 8.

Management of paraneoplastic syndromes in lung cancer.

Paraneoplastic syndromes are common complications of lung cancer. Although most frequently associated with advanced disease, paraneoplastic syndromes may also occur at early stages. Occasionally, the paraneoplastic syndrome may be the presenting symptom of lung cancer. For most paraneoplastic syndromes, the best treatment is to treat the underlying malignancy. However, in many cases, treatment of moderate efficacy or urgent therapy is required. Specific recommendations for the management of the most common paraneoplastic syndromes, including cachexia, hypercalcemia, and hyponatremia, are provided.

A randomized trial of yogurt for prevention of antibiotic-associated diarrhea.

Antibiotic-associated diarrhea (AAD) is the most common adverse effect of antibiotic therapy. Our aim was to determine the effectiveness of a dietary supplement of yogurt for prevention of AAD. Two hundred two hospitalized patients receiving oral or intravenous antibiotics were randomized to receive or not receive a dietary yogurt supplement, consisting of 227 grams of commercial yogurt, and followed for 8 days. Mean age of the study group was 70 years and 43% were male. Compliance and 8-day follow-up were 85% and 91%, respectively. Patients receiving yogurt reported less frequent diarrhea (12% vs 24%; P = 0.04), and significantly less total diarrhea] days (23 vs 60). The cumulative proportions of patients without diarrhea were significantly different (P = 0.02) between patients receiving and not receiving yogurt. For conclusion, dietary supplementation with yogurt is a simple, effective, and safe treatment that decreases the incidence and duration of AAD.